The purpose of this study was to examine the effects of alcohol intoxication and its interaction with contextual or situation (partner familiarity) and individual differences variables (effortful control, urgency, and whether taking pre-exposure prophylaxis (PrEP) medication) on sexual behaviors in men who have sex with men (MSM), a subgroup for whom HIV continues to be a major public health problem in the U.S. The participants were 236 men recruited from two northeastern U.S. cities and aged 21-50 years, M = 27.8). These men participated in a 6-week (two 3-week sampling bursts) experience sampling method (ESM) study. The ESM data were collected via use of software installed on the participant's own or study-provided mobile phone. Individual differences variables were measured by participants' completing questionnaires measuring effortful control and urgency, and the participant's self-report of whether he was currently taking PrEP. The ESM data pertained to sexual behavior as well as situation variables of familiarity of relevant sexual partners and number of standard alcohol drinks consumed. The results generally were consistent with hypotheses, as alcohol intoxication showed a curvilinear relation to the occurrence of condomless anal intercourse. Furthermore, the likelihood of occurrence of condomless anal sex increased with increased familiarity of the sexual partner. Similarly, taking PrEP increased the likelihood of occurrence of condomless anal sex. At the same time, alcohol's effects were moderated by all three individual differences variables as expected, but the prediction that partner familiarity would moderate alcohol's effects on the occurrence of condomless sex was not supported. Clinical implications of the findings center on the application of the data to HIV prevention programs toward inclusion of more empirically supported, nuanced information on the relation between acute alcohol intoxication and sexual behavior. Directions for further research address the need for additional testing and refinement of a person × situation approach to alcohol and sexual behavior. Furthermore, it is argued that it is important to refine further the concept of sexual risk in the context of taking PrEP and to conduct more detailed, multivariate studies of the relation between taking PrEP and patterns of sexual behavior.